Cargando…

Discovery of Pinostrobin as a Melanogenic Agent in cAMP/PKA and p38 MAPK Signaling Pathway

Melanogenesis is the process of melanin synthesis to protect the skin against ultraviolet radiation and other external stresses. The loss of skin pigmentation is closely related to depigmented skin disorders. The melanogenic effects of pinostrobin, an active flavanone found in honey, were evaluated....

Descripción completa

Detalles Bibliográficos
Autores principales: Yoon, Jeong-Hyun, Youn, Kumju, Jun, Mira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9504415/
https://www.ncbi.nlm.nih.gov/pubmed/36145089
http://dx.doi.org/10.3390/nu14183713
_version_ 1784796210181177344
author Yoon, Jeong-Hyun
Youn, Kumju
Jun, Mira
author_facet Yoon, Jeong-Hyun
Youn, Kumju
Jun, Mira
author_sort Yoon, Jeong-Hyun
collection PubMed
description Melanogenesis is the process of melanin synthesis to protect the skin against ultraviolet radiation and other external stresses. The loss of skin pigmentation is closely related to depigmented skin disorders. The melanogenic effects of pinostrobin, an active flavanone found in honey, were evaluated. B16F10 cells were used for melanin content, tyrosinase activity, and the expression of melanogenesis-related markers. Moreover, computational simulations were performed to predict docking and pharmacokinetics. Pinostrobin increased melanin levels and tyrosinase activity by stimulating the expression of melanogenic regulatory factors including tyrosinase, tyrosinase-related protein (TRP) 1 and microphthalmia transcription factor (MITF). Specifically, the phosphorylation of cAMP response element binding (CREB) involved in the MITF activation was augmented by pinostrobin. Moreover, the compound upregulated the β-catenin by cAMP/PKA-mediated GSK-3β inactivation. Co-treatment with a PKA inhibitor, inhibited melanin production, tyrosinase activity, and expression of MITF, p-CREB, p-GSK-3β and p-β-catenin, demonstrating that pinostrobin-stimulated melanogenesis was closely related to cAMP/PKA signaling pathway. Furthermore, the combination of pinostrobin and a specific p38 inhibitor, showed that MITF upregulation by pinostrobin was partly associated with the p38 signaling pathway. Docking simulation exhibited that the oxygen group at C-4 and the hydroxyl group at C-5 of pinostrobin may play an essential role in melanogenesis. In silico analysis revealed that pinostrobin had the optimal pharmacokinetic profiles including gastrointestinal absorption, skin permeability, and inhibition of cytochrome (CYP) enzymes. From the present results, it might be suggested that pinostrobin could be useful as a potent and safe melanogenic agent in the depigmentation disorder, vitiligo.
format Online
Article
Text
id pubmed-9504415
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-95044152022-09-24 Discovery of Pinostrobin as a Melanogenic Agent in cAMP/PKA and p38 MAPK Signaling Pathway Yoon, Jeong-Hyun Youn, Kumju Jun, Mira Nutrients Article Melanogenesis is the process of melanin synthesis to protect the skin against ultraviolet radiation and other external stresses. The loss of skin pigmentation is closely related to depigmented skin disorders. The melanogenic effects of pinostrobin, an active flavanone found in honey, were evaluated. B16F10 cells were used for melanin content, tyrosinase activity, and the expression of melanogenesis-related markers. Moreover, computational simulations were performed to predict docking and pharmacokinetics. Pinostrobin increased melanin levels and tyrosinase activity by stimulating the expression of melanogenic regulatory factors including tyrosinase, tyrosinase-related protein (TRP) 1 and microphthalmia transcription factor (MITF). Specifically, the phosphorylation of cAMP response element binding (CREB) involved in the MITF activation was augmented by pinostrobin. Moreover, the compound upregulated the β-catenin by cAMP/PKA-mediated GSK-3β inactivation. Co-treatment with a PKA inhibitor, inhibited melanin production, tyrosinase activity, and expression of MITF, p-CREB, p-GSK-3β and p-β-catenin, demonstrating that pinostrobin-stimulated melanogenesis was closely related to cAMP/PKA signaling pathway. Furthermore, the combination of pinostrobin and a specific p38 inhibitor, showed that MITF upregulation by pinostrobin was partly associated with the p38 signaling pathway. Docking simulation exhibited that the oxygen group at C-4 and the hydroxyl group at C-5 of pinostrobin may play an essential role in melanogenesis. In silico analysis revealed that pinostrobin had the optimal pharmacokinetic profiles including gastrointestinal absorption, skin permeability, and inhibition of cytochrome (CYP) enzymes. From the present results, it might be suggested that pinostrobin could be useful as a potent and safe melanogenic agent in the depigmentation disorder, vitiligo. MDPI 2022-09-09 /pmc/articles/PMC9504415/ /pubmed/36145089 http://dx.doi.org/10.3390/nu14183713 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yoon, Jeong-Hyun
Youn, Kumju
Jun, Mira
Discovery of Pinostrobin as a Melanogenic Agent in cAMP/PKA and p38 MAPK Signaling Pathway
title Discovery of Pinostrobin as a Melanogenic Agent in cAMP/PKA and p38 MAPK Signaling Pathway
title_full Discovery of Pinostrobin as a Melanogenic Agent in cAMP/PKA and p38 MAPK Signaling Pathway
title_fullStr Discovery of Pinostrobin as a Melanogenic Agent in cAMP/PKA and p38 MAPK Signaling Pathway
title_full_unstemmed Discovery of Pinostrobin as a Melanogenic Agent in cAMP/PKA and p38 MAPK Signaling Pathway
title_short Discovery of Pinostrobin as a Melanogenic Agent in cAMP/PKA and p38 MAPK Signaling Pathway
title_sort discovery of pinostrobin as a melanogenic agent in camp/pka and p38 mapk signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9504415/
https://www.ncbi.nlm.nih.gov/pubmed/36145089
http://dx.doi.org/10.3390/nu14183713
work_keys_str_mv AT yoonjeonghyun discoveryofpinostrobinasamelanogenicagentincamppkaandp38mapksignalingpathway
AT younkumju discoveryofpinostrobinasamelanogenicagentincamppkaandp38mapksignalingpathway
AT junmira discoveryofpinostrobinasamelanogenicagentincamppkaandp38mapksignalingpathway